This invention relates to NMR imaging apparatus and methods. More specifically, this invention relates to apparatus and methods of obtaining spatially resolved, high resolution spectra of low concentration substances in tissue containing a large solvent peak.
Nuclear Magnetic Resonance (NMR) is a very useful tool in medical diagnosis and chemical experimentation. A sample to be analyzed is placed in a static homogeneous magnetic field. The sample contains nuclei which are spinning at a given rate which produces an angular magnetic moment for each nucleus. The static magnetic field has the effect of aligning the spin-axis of each nucleus with or against the magnetic field. The sample is then bombarded with RF energy which excites the nuclei causing them to "flip" to higher energy states. As the nuclei flip, they absorb RF energy which is then given off as the nuclei relax. This energy emission (the free induction decay) is observed using an RF receiver. Each set of nuclei will emit energy at a characteristic frequency, known as resonance. Therefore, by analyzing the frequency spectrum of the observed signal, the presence of a particular set of nuclei in the sample can be determined. The resonant frequency may be shifted by changing the chemical environment in which the nuclei are located. This is known as a chemical shift and is important in distinguishing like nuclei located in different chemical compounds. Problems exist in that many samples contain nuclei with overlapping or near identical resonant frequencies. Also, a wide variety of resonances may be present in the sample while the experimentor wishes only to observe one of the resonances. These problems may be compounded when an attempt is made to take the observed frequency spectrum and create a two or three-dimensional image of the chemical in the sample.
Many methods exist for analyzing and mapping a specimen using NMR techniques. For example U.S. Pat. No. 4,431,968 to Edelstein et al describes a method of three-dimensional imaging in a thick-slab sample by using frequency selective RF pulses to excite the sample and then applying pulsed gradient magnetic fields to phase encode spatial information about the sample. The resultant NMR signal, after Fourier analysis, provides a three-dimensional image of the sample including nuclear spin density and relaxation time information.
The "filtered back-projection reconstruction" method described by P.C. Lauterbur in "Image Formation by Induced Local Interactions: Examples Employing NMR", Nature, 242, pp. 190-191 (1973), utilizes a series of image projections taken at many angles around a plane passing through the object. Each projection contains some unique information about the object and, by suitable mathematical manipulation, the information can be used to form an image of the object.
The "sensitive point" method described by W.S. Hinshaw in "Image Formation by Nuclear Magnetic Resonance: The Sensitive-Point Method", Journal of Applied Physics, Vol. 47, p. 3709 (1976), applies alternate magnetic field gradients along all three orthogonal axes of the sample. Thus, there exists a point in the sample where no magnetic field fluctuations exist and the conditions for resonance are satisfied. This point is then scanned through the sample in raster fashion and the returning signals are recorded.
The "field focusing NMR (FONAR)" method described by R. Damadian, L. Minkoff, M. Goldsmith and J. D. Koutcher in "Field Focusing Nuclear Magnetic Resonance (FONAR): Visualization of a Tumor in a Live Animal", Science, Vol. 194, pp. 1430-1432 (1976), utilizes a saddle-shaped magnetic field to provide a resonant sensitive area in the sample. Following a frequency selective RF excitation, appreciable signal is obtained only from the region of the saddle point. Again, the sensitive point can be electro-magnetically scanned through the sample.
The "depth pulse" method described by M. R. Bendall in "Depth and Refocusing Pulses Designed for Multipulse NMR with Surface Coils", Journal of Magnetic Resonance, 53, pp. 365-385 (1983), utilizes a surface coil to obtain spatial discrimination. When a surface coil is used, the RF excitation pulse angle decreases rapidly as it penetrates the sample. The length of the RF pulse and hence the pulse angle can be varied and the signal intensity obtained from any sample region will be related to the pulse angle. Consequently, the location of maximum signal intensity will indicate a specific location in the sample. The RF pulses can be varied and location information can be obtained from throughout the sample.
The "4-D Fourier spectroscopic imaging" method as described by A.A. Maudsley, S.K. Hilal, W. H. Perman, and H.E. Simon in "Spatially Resolved High Resolution Spectroscopy by `Four-Dimensional` NMR", Journal of Magnetic Resonance, 51, pp. 147-152 (1983) produces a full set of information from all parts of the sample in a single experiment. First a broad frequency-band pulse is applied to a sample and the free induction decay is allowed to evolve in the presence of a magnetic field gradient, the amplitude of which is varied along the x, y and z axes. Next a 180.degree. pulse is applied and the spin echo is observed. During the second echo evolution period, no field gradients are applied and the spins evolve only under the local interactions, providing a high resolution spectrum after Fourier transformation of the detected signal. The amplitudes of the field gradients are varied and a complete four dimensional time data set is obtained. A four-dimensional Fourier transformation results in an NMR spectrum indicating the presence of nuclear spins at each spatial location.
The methods described above do not appear to be capable of yielding a high resolution .sup.1 H NMR image of substances, particularly metabolites such as lactate, which exist in low concentrations in tissue samples having a high water and lipid concentration. This is so because each of these methods either does not adequately suppress the water and lipid signals, or does not adequately edit the received signal so as to unambiguously locate the substance in the sample, or does not image the entire sample volume but only "looks at" slices or thick slabs of the sample.
When a sample containing a substance of interest, such as lactate, is subjected to the NMR imaging methods described above, the lactate proton resonances are often not detectable in the presence of the large water resonance. This is a consequence of the dynamic range problem associated with the very high concentrations of tissue water and lipid as compared to the low concentration of lactate. Thus, it is difficult to determine unambiguously the presence and location of the lactate in the sample. When the water is suppressed, the presence of the metabolite must be unambigiously determined by editing the spectra to eliminate signals emanating from lipid and other metabolites not of interest. Therefore, known imaging methods require great sensitivity in the measuring equipment and a great amount of computation in order to perform the chemical shift transform required to obtain satisfactory imaging information from the sample.